Single-Dose Ketamine Followed by Daily <span style="font-variant:small-caps; ">d</span>-Cycloserine in Treatment-Resistant Bipolar Depression

Abstract

Analysis Follow--UpReceived ketamine (n= 8) EnrollmentReceived D-cycloserine (n= 8)

Ketamine for Treatment-Resistant Unipolar and Bipolar Major Depression: Critical Review and Implications for Clinical Practice

“…Some controlled investigations have provided proof-of-concept for studying the antidepressive effectiveness of add-on riluzole and D-cycloserine following acute treatment with ketamine. [87,88] However, this evidence is only preliminary and, as reviewed recently, these and other NMDA receptor modulators have been tested individually for their acute antidepressive effects but have not been shown to be as consistently effective as ketamine for treating depression in adults. [42,49] The administration of repeated ketamine infusions to sustain initial positive responses has some appeal, since it is analogous to the use of maintenance pharmacotherapy or ECT.…”

Ketamine: 50 Years of Modulating the Mind

“…Even a single-dose of ketamine may cause rapid antidepressant effects in otherwise treatment-resistant cases of bipolar (DiazGranados et al, 2010b; Ibrahim et al, 2011; Kantrowitz et al, 2015) and major depression (Zarate et al, 2006; Murrough et al, 2013). Remarkably, this also includes the acute reduction of suicidal ideation (DiazGranados et al, 2010a; Larkin and Beautrais, 2011; Zigman and Blier, 2013; Murrough et al, 2015).…”

Maintaining the Initial Clinical Response After Ketamine in Bipolar and Unipolar Depression: An Important Next-Step Challenge

“…In previous studies with IV ketamine, depressive relapse occurred after 1-3 weeks, although with high individual variability. Four of the 7 bipolar depressed subjects treated by Kantrowitz and colleagues 27 were still in remission after 8 weeks of additional treatment with d-cycloserine. The clinical improvement at week 8 was correlated with the magnitude of improvement at 24 hours after ketamine, 27 which suggests the 2 treatments may be indeed synergistic and that d-cycloserine may prolong the initial clinical response after ketamine.…”

“…d-Cycloserine has several advantages: it can be administered orally and it has established safety and tolerability in long-term use. 28 In the 7 bipolar depressed subjects treated by Kantrowitz and colleagues, 27 d-cycloserine appears to prevent the relapse of depressive symptomatology after the initial IV ketamine dose. In previous studies with IV ketamine, depressive relapse occurred after 1-3 weeks, although with high individual variability.…”

“…Our enthusiasm needs to be tempered by the very small study sample and the open design of the current study, 27 which limit our ability to draw any definitive conclusions. However this result is important, and, if replicated in a large randomized controlled study, will represent a major advance in our field.…”